Diazine derivatives



Patented Jan. 11, 1944 2 339,060 DIAZINE DERIVATIVES lio and James W.Underwood;

Pittsfield, Masa, assignors to Gen al Company, a corporation of New} 1-5 1 pplication August 26,4 5, I Serial No. 456,263

No Drawing.

18 Claims. (01. 260-251) a If 4 be represented by the following generalformula;

where R represents a member of the class consisting of hydrogen andmonovalent hydrocarbon and substituted hydrocarbon radicals, moreparticularly halo-hydrocarbon radicals, Y represents a polyacyl radicalof a polycarboxylic acid, more particularly an aliphatic or an aromaticpolycarboxylic acid, and n is an integer having a value equal to thevalency of the acyl radical of Y. In the compounds represented by theabove formula and by similar formulas hereafter given, one nitrogen atomof the grouping -NH--NI-I- is linked to a carbon atom of the diazi'nenucleus and the other nitrogen atom is linked to a carbon atom of acarbonyl grouping of the polyacyl radical represented by Y.

Illustrative examples of radicals that R in the above formula mayrepresent are: aliphatic (e. g., methyl, ethyl, propyl, isopropyl,butyl, secondary butyl, isobutyl, butenyl, amyl, isoamyl, hexyl, octyl,allyl, methallyl, ethallyl, crotyl, etc.), including cycloaliphatic (e.g., cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl,etc.) aryl (e. g., phenyl, diphenyl or xenyl, naphthyl, anthracyl, etc);aliphatic-substituted aryl (e. g., tolyl, xylyl, ethylphenyl,propylphenyl, isopropylphenyl, allylphenyl, 2-buteny1phenyl,tertiary-butylphenyl, eta); aryl-substituted aliphatic (e. g., benzyl,phenylethyl, cinnamyl, pherrvipropyl, etc.) and their homologues, aswell as those groups with one or more of their hydrogen atomssubstituted by, for example, a halogen, more particularly chlorine,bromine, fluorine or iodine. Specific examples of halogeno-substitutedhydrocarbon radicals that R inthe above formula may represent are:chloromethyl, chloroethyl, chlorophenyl, dichlorophenyl, ethylchlorophenyl, chlorocyclohexyl, phenyl chloroethyl, bromoethyl,bromopropyl, iodophenyl, phenyl, bromotolyl, etc. Preferably R inFormula I is hydrogen, in which case the compounds may be represented bythe general formula:

where a and-Y -ha ve-the' same 'm'eaninngs as given above with referenceto Formula Illustrative examples of polyacyl radicals that YinFormulas-I and II may represent -are:' aliphatic polyacyl ie.g1,=oxalyl,' malonyl, succinyl, glutaryl, adipyl, tricarballylyhetc.)including unsaturated aliphatic polyacyl, e. g., maleyl, fumaryl,glutaconyl; itaconyl, citraconyl, mesa conyl, glutinyl, aconityl,muconyl; etc., and'aromatic' polyacyl, e. g", "phthalyL; naphthalyl,"tnmesyl, chlorophthalyi, bromophthalyl, isophthal'yl,-terephthalyl,--'etc. Preferably Y is a succinyl or aphthalyl radical; I

The'new compounds ot this invention may-be used, for example, aspharmaceuticals; plasticizers and as'intermediates in the preparation ofI derivatives "thereof; e; 'g., methylol, methylene, etc., derivativesof the individual compound-embraced by Formula I. "These new compoundsare especially valuable in the preparation of synthetic resinouscompositions. Thus, they m'ay be condensed with, for instance,aldehydes', includ-- ing polymeric aldehydes, hydroxyaldehydes andaldehyde-addition products, to yield condensation products of particularutility in the plastics and coating arts. Such condensation products aremore fully described and are specifically claimed in our copendingapplication Serial No. 461,768, filed October 12, 1942, and assigned tothe same assignee as the present invention.

Various methods can be employed to produce the chemical compounds ofthis invention. One' suitable method comprises effecting reaction, inthe resence of a hydrohalide acceptor, between a diazine derivativecorresponding to the general formula It, [R-C/ N 1 m a (BEN-)5 C--Nn-NH,

' and an acyl halide corresponding to the general formula IV Yxnz-hydrazino 4,6-diamino pyrimidine 4,-hydrazino 2,6-diamino pyrimidine(G-hydrazino 2,4-diamino pyrimidine) 2-hydrazino 4,6-di-(methylamino)pyrimidine 4-hydrazino 2,6- di-(methylamino) pyrimidine Z-hydrazino4,6-di-(methylamino) pyrimidine z-hydrazino 4,6-di-(chloroethylamino)4-hydrazino 2,6-di-(propylamino) pyrimidine 2-hydrazino4,6-di-(propenylamino) pyrimidine 2-hydrazino 4,6-di-(isobutylamino)pyrimidine 2-hydrazino 4,6-dianilino pyrimidine '4-hydrazino2,6-dianilino pyrimidine 2-hydrazino 4,6-ditoluido pyrimidined-hydrazino 2,6-ditoluido pyrimidine 4-hydrazino 2,6-dixylidinopyrimidine 4-hydrazino 2.6-di-(benzylamino) pyrimidine 2-hydrazino4,6-di-(ethylanilino) pyrimidine 2-hydrazino 4,6-di-(cyclopentylamino)pyrimidine Z-hydrazino 4,6-diamino S-methyl pyrimidine Z-hydrazino4,6-diamino S-phenyl pyrimidine 2-hydrazino 4,6-dlanilino fi-methylpyrimidine 2-hydrazino 4,6-dianilino 5-phenyl pyrimidine 2-hydrazino4-methylamino 6-amino pyrimidine z-hydrazino 4-fluoroanilino 6-aminopyrimidine 2-hydrazino d-methylamino 6-anillno pyrimidine d-hydrazino2,6-di-(methylamino) 5-tolyl pyrimidine 2-hydrazino -cyclohexylamino5-benzyl 6.-: ;y]l-- dino pyrimidine py dine 2-hydrazlno4,6-di-(chloroanilino) pyrimidine 4-hydrazino 2,6-di-(bromoanilino)pyrimidine z-hydrazino 4,6-di-(iodotoluido) pyrimidine z-hydrazino4,'6-di-(bromopropylamino) pyrimidine fl-hydrazino 4,6-di- (methylamino)fi-chlorophenyl pyrimidine 4-hydrazino 2,6-di-(allylamino) 5-allylpyrimidine I 2-hydrazino 4,6-di-(octylamino) 5-cyclohexyl pyrimidine4-hydrazino 2,6-di-(cyclohexenylamino) pyrimidine 2-hydrazino4,6-di-(phenethylamino) pyrimidine 4-hydrazino 2,6-di-(cinnamylamino)pyrimidine 2-hydrazino 4,6-di-(butenylamino) 5-xenyl pyrimidineIllustrative examples of acyl halides embraced by Formula IV that may beused, depending upon the desired end-product. are:

Various hydrohalide acceptors may be employed butwe prefer to use atertiary base, e. 3.,

tertiary amines such as trialkyl (e. g., trimethyl,

triethyl. tripropyl, tributyl. etc.) amines, triaryl (e; g., triphenyl.tritolyl, etc.) amines. pyridine, dimethyl aniline, etc. The reactionbetween the hydrazino-substituted diazine and the acyl halide may becarried out in any suitable manner, but.

preferably is effected in the presence of a suitable solvent or mixtureof solvents. It is advisable to use an anhydrous. medium, e. g., ether,benzene, toluene. etc., because of the high degree.

where X represents a halogen atom, and n, Y and B have the same meaningsas given above with reference to Formula I, each halogen atomrepresented by x being linked directly to a carbon atom of a carbonylgroup of the polyacyl radical re resented by Y. 7

Another method that may be employed in preparing the new chemicalcompounds of this invention comprises efiecting reaction between amonohalogeno diamino [(-NHRh] pyrimidine and a polyhydrazide of apolycarboxylic acid. This reaction preferably is carried out in thepresence of a suitable solvent or mixture or solvents. A hydrohalideacceptor also preferably is present.

In order that those skilled in theart better may understand how thepresent invention may be carried into eifect, the following examples aregiven by way of illustration and not by way of limitation. All parts areby weight.

7 Example 1 This example illustrates the preparation of bis-[2,6-di(methylamino) pYrimidyl-d hydrazinocarbonyl], which also may benamed bis- [2,4-di- (methylamino)' pyrimidyl-6 hydrazinocarbonyll.

Approx.

2 Parts mol ratio l-hydrazino 2,6-di-(methylamino) pyrimidine. Oxalylchloride 57 1 Pyridine 71 2 and dried. A yield of 158 parts of purifiedand dried product was obtained.

Example 2 This example illustrates the preparation of bis-[2,6-di-(methylamino) pyrimidyl-4 hydrazinecarbonyl] methane.

Approx.

PM moi ratio d-hydravlno zt-di-(methylmnino) pyrimidino.. 150 Maionylchloride 675:1.

7 Example 3 Example 5 Bis-(Zfi-diarnino pyrimidy1-4 hydrazinocarbonyl)is prepared in essentially the same manner as described under Example 1with the exception that 125 parts of 4-hydrazino 2,6-diamino pyrimidineareused in place of 150 parts of 4-hydrazino 2,6-di- (methylamino)pyrimidine.

Example 6 Bis-(4,6-diamino pyrimidyl-2 hydrazinocarbonyl) methane isprepared in essentially the same manner as described under Example 2with the exception that 125 parts of 2-hydrazino 4,6-' diaminopyrimidine are used instead of 150 parts of d-hydrazino 2,6-di-(methylamino) pyrimidine.

Example 7 Alpha,beta.gamma-tri- [2,6- di -(methylamino) pyrimidy1-4hydrazinocarbonyl] propane is prepared in essentially the same manner asdescribed under Example 1 with the exception that 69 parts oftricarballylyl chloride are used instea or 57 parts of oxalyl'chloride.

Example 8 A bis-(diamino pyrimidyi hydrazinocarbonyl) benzene, moreparticularly a bis- (4,6-dlamino pyrimidyl-2 hydrazinocarbonyl) benzeneor a bis- (2,6-diamino pyrimidyl-4 hydrazinocarbonyl) benzene, isprepared in essentially the same manner as described under Example 1with the exeeption that 125 parts of 2-hydrazino 4,6-diamino pyrimidineor of 4-hydrazino 2,6-diamin0 pyrimidine are used in place of 150 partsof 4-hydrazino 2,6-di-(methylamino) pyrimidine and 91.2 parts of aphthalyl chloride (ortho-phthalyl dichloride, iso-phthalyl dichloride orterephthalyl dichloride) are used in place of 57 parts of oxalylchloride.

Example 9 A bis-(diamino pyrimidyl hydrazinocarbonyl) ethane, moreparticularly an alpha,beta-bis-(4,6- diamino pyrimidyl-2hydrazinocarbonyl) ethane or an alpha,beta-bis-(2,6-diamino pyrimidyl-4hydrazinocarbonyl) ethane. is prepared in essentially the same manner asdescribed under Exampie 1 with the exception that 125 parts of 2- dr ino4, -diamino pyrimidine or of d-hydrazi'no 2.6-diamino pyrimidine areused instead of 150 parts of 4-hydrazino 2,6-di-(methylamino) pyrimidineand 69.6 parts of succinyl chloride are used in place of 57 parts oroxalyl chloride.

Illustrative examples of other chemical compounds embraced by Formula Ithat may be produced in accordance with the present invention are listedbelow, including both poly-(diammo pyrimidyl hydrazinocarbonyl)-substituted aliphatic hydrocarbons, more particularly bis-(diaminopyrimidyl hydrazinocarbonyl) alkanes and alkenes, and poly-(diaminopyrimidyl hydrazinecarbonyl) -subs tituted aromatic hydrocarbons.

Bis-(4,6-diamino fi-methyl pyrimidyl-2 hydrazinocarbonyl) Bis-(2,6-diamino pyrimidyl-4 hydrazinocarbonyl) methane Bis-(4,6-diaminoS-phenyl pyrimidy1-2 hydrazi- -nocarbonyl) methane Alrihabeta-bis-[4,6-di- (methylamino) dyl-2 hydrazinocarbonyl] ethane Alpha,beta-bis-[4,6-di-(ethylamino) DYrimidy1-2 hydrazinocarbonyl] ethaneAlpha,beta-bis-[4,6-di-(propenvlamino) pyrimidyl-2 hydrazinocarbcnyl]ethane Alpha,beta-bis-[4,6-di-(cyclohexylamino) py midyl-2hydrazinocarbonyl] ethane Alpha,beta-bis-(2,6-dianilin0 pyrimidyl-4hydrazinocarbonyl) ethane Bis-(4,6diamino pyri 'd'yl-2hydrazinocarbonyl) bromonaphthalene Alpha,beta-bis-[2,6-di-(fluoroanilino) pyrimidyl 4 hydrazinocarbonyl] ethaneA1pha,beta-bis- (2,6-dito1uido pyrimidyl-4 hydrazinocarbonyl) ethaneA1pha,betabis-(2,6-dixylidino pyrimidyl-4 hydrazinocarbonyl) ethaneA1pha,beta-bis- [2,6-di- (benzylamlno) py midyl- 4 hydrazinocarbonyllethane.

Alpha,beta-bis- [2,6-di- (ethylanilino) pyrimidyl-4 hydrazinocarbonyl]ethane Alpha,gamma-bis-(4,6-diannno pyrimidy1-2 hydrazinocarbonyl)propane A1pha ,omega-bis- (4,6-diamino 5-ethyl pyrimidyl- 2hydrazinocarbonyl) butane Alpha,beta-bis-(4,6-diamino pyrimidyl-2hydrazinocarbonyl) propene Alpha,beta-bi s-(4,6-diamino pyrimidyl-2hydrazinocarbonyl) ethane Alpha,beta-dis-(4-methylamino G-aminopyrimidyl-2 hydrazinocarbonyl) ethane 4 Alpha,beta-bis-(4-anilinoG-amino pyrimidyl-2 hydrazinocarbonyl) ethane Alpha,beta-bis-(4-anilino6-methylamino pyrimidyl-2 hydrazinocarbonyl) ethane Alpha,beta-bis-[2,6-di- (methylamino 5-tolyl pyrimidyl-4 hydrazinocarbonyl] ethaneBis-[4,6-di-(methylamino) midyl-z hydrazinoearbonyl] benzenesBis-(4,6-dianilino 5-phenyl pyrlmidyl-Z hydrazinocarbonyl) benzenesBis-(4,6-diamino pyrimidyl-2 hydrazinocarbonyl) toluenes Bis-(4,6-diamino pyrimidyl-2 hydrazinocarbonyl) xylenes py mBis-(4,6-dlamino pyrlmidyl-2 hydrazinocarbonyl) naphthalenes Bis-[4,6-di-(iodoanilino) .pyrlmidyl-2 hydrazinecarbonyll benzenesAlpha,beta-bis- [2,6-di- (ethyiamino) -xenyl pyrimidyl-4hydrazinocarbonyl] ethane Bis- [4,6-di- (bromotoluido) pyrimidylz'hydrazinocarbonyll methane Alphapmega-bis-izdcyclohexylamino)5-chloroethyl 6-anilinopyrimidyl-4 hydrazinocarbonyll phenylbutaneAlpha,beta,gamma-tri-(4,6-dlamino pyrimidyl-2 hydrazinocarbony propane1,3,5-tri-(4',6'-diamino pyrimidyl-ll' hydrazinecarbonyl) benzenes- Bis-(4,6-diamino pyrimidyl 2 hydrazinocarb'onyl) chlorobenzenes Bis-[2,6-di- (chloromethylamino) 5-ethyl pyrimidyl-4 hydrazinocarbonyll Bis-[4,6-di- (bromoanilino) nocarbonyl] methane Bis- [2,6-di-(a1lylamin0)hydrazinoca'rbonyl] methane g Bis- [4,6-di-(cyclohexylamino) pyrimidyl-2hydrazinocarbonyl] ethanes Bis-[2,6-di-(octylamino) 5-cyclohexylpyrimidyl- 4 hydrazinocarbonyll propanes 5-pheny1 pyrimidyl-4Bis-[4,6-di-(fluoroanilino) pyrimidyl-2 meal In a manner similar to thatdescribed above with particular reference to the production orpoly-(pyrimidyl hydrazine) that is, poly-(1,3-diazinyl hydrazino),derivatives of polycarboxylic acids, corresponding derivatives of the'1,2-'dlazines (pyridazines) and of the lA-diazines (pyrazines) ay beprepared.

What we claim as new and desire to secure by Letters Patent of theUnited States-is:

1. Chemical compounds corresponding general formula to the 'r. [we] #1where R represents a member of the class consisting of hydrogen andmonovalent hydrocarbon and halo-hydrocarbon radicals, Y represents apolyacyl radical of a polycarboxylic acid, and n is an integer having avalue .equal to the valency oi the polyacyl radical of Y. one nitrogenatom pyrimidyl-2 hydranof the grouping -NHNH'- in the above formulabeing linked to a carbon atom oi the diazine nucleus and the othernitrogen atom being linked to a carbon atom of a carbonyl grouping ofthe polyacyl radical represented by Y.

2. Chemical compounds corresponding to the general formula lama} L I h LN I n where R represents hydrogen, Y represents a polyacyl radical ofapolycarboxylic acid. and n is an integer having a value'equal to thevalency of the polyacyl radical o f- Y, one nitrogen atom of thegrouping NH--NH- in the above formula being linked to a carbon atom ofthe dlazine nucleus and the other nitrogen ato m'being linked to acarbon atom of a carbonyl grouping of the polyacyl radical representedby Y.

3. Chemical compounds corresponding to the general formula i [a a 4where R represents a member or the class consisting of hydrogen andmonovalent hydrocarbon and halo-hydrocarbon radicals, Y represents a;polyacyl radical of an aliphatic polycarboxylic acid, and n is aninteger having a value equal to the valency of the polyacyl radical ofY, one mtrogen atom of the grouping -NHNH in the above-formula beinglinked to a carbon atom of S-butyl pyrimidy li hythe diazine nucleus andthe other nitrogen atom being linked to a carbon atom of a carbonylgrouping of the polyacyl radical represented by Y. 4. Chemical compoundscorresponding to the general formula i i R 0 where R represents a memberof the class consisting of hydrogen and monovalent hydrocarbon andhalo-hydrocarbon radicals, Y represents a polyacyl radical of anaromatic polycarboxylic acid, and at is an integer having a value equalto the valency of the polyacyl radical of Y, one nitrogen atom' of thegrouping '--NH--NH- in the above formula being linked to a carbon atomof ,the dia'zine nucleus and the other nitrogen atom being linked to acarbon atom of a carbonyl grouping of the polyacyl radical representedby Y. 5. Chemical compounds corresponding to the general formula where Rrepresents hydrogen, Y represents a polyacyl radical of an aliphaticpolycarboxylic acid, and 1; is an integer having a value equal to thevalency of the' polyacyl radical of Y, one nitrogen atom of the grouping-NHNH- in the above formula being linked to a carbon atom where Rrepresents hydrogen, Y represents a polyacyl radical of an aromaticpolycarboxylic acid, and n is an integer having a value equal to thevalency of the polyacyl radical of Y, one nitrogen atom of thegrouping'-NHNH in the above formula being linked to a carbon atom of thediazine nucleus and the other nitrogen atom being linked to a carbonatom of a carbonyl grouping of the polyacyl radical represented byY.

7. A poly-(diamino. pyrimidyl hydrazinocarbonyl) -substituted aliphatichydrocarbon.

8. A bis-(diamino pyrimidyl hydrazinocarbonyl) alkane.

9. A poly-(diamino pyrimidyl hydrazinocarbonyl) -substituted aromatichydrocarbon.

10. A bis-(diamino pyrimidyl hydrazinocarbonyl) benzene.

11. A bis-(diamino pyrimidyl hydrazinoc'arbonyl) ethane.

12. Alpha,beta-bls-(2,6-diamino pyrimidyl-4 hydrazinocarbonyl) ethane.

13. A bis-[di- (methylamino) pyrimidyl hydrazinocarbonyl].

14. Bis- [2,6-di-(methylamino) pyrimidyl-4 hydrazinocarbonyll.

15. The method of preparing chemical compounds corresponding to thegeneral formula 5 [RC/ \N (RHN} g 4 NHNH Y L L a J where R represents amember of the class consisting of hydrogen and monovalent hydrocarbonand halo-hydrocarbon radicals, Y represents a polyacyl radical of apolycarboxylic acid, and n is an integer having a value equal to thevalency of the polyacyl radical of Y, -NH-NH-- in the above formulabeing linked to a carbon atom of the diazine nucleus and the othernitrogen atom being linked to a carbon atom of a carbonyl grouping ofthe polyacyl radical represented by Y. said method comprising effectingreaction, in the presence of a hydrohalide acceptor, between a compoundcorresponding to the general formula Lac L and an acyl halidecorresponding to the general formula where X represents a halogen atom,and n, Y and R have the same meaiflngs as given above, each halogen atomrepresented by X being linked directly to a carbon atom ofa carbonylgroup of the polyacyl'radical represented by Y.

16. The-method of preparing chemical compounds corresponding to thegeneral formula n-o N (mm),- a \N'H--NH L N J where R representshydrogen, Y- represents a polyacyl radical of a polycarboxylic acid, andn is an integer having a value equal to the valency oi the polyacylradical of Y, one nitrogen atom of the grouping --NH-NH- in the aboveformula being linked to a carbon atom of the diazine nucleus and theother nitrogen atom being linked to a carbon atom ofa carbonyl groupingof the 'polyacyl radical represented by Y, said method comprisingeffecting reaction, in the presence of a tertiary base, between acompound corresponding to the general formula L J and an acyl halidecorresponding to the general formula YXn where X represents a chlorineatom, and n, Y"

and R have the same meanings as given above, each chlorine atomrepresented by X being linked directly to a carbon atom of a carbonylgroup of the polyacyl radical represented by Y.

17. The method oi. preparing a bis-[di- (methylamino) pyrimidylhydrazinocarbonyl] which comprises effecting reaction, in the presenceof a hydrohalide acceptor, between oxalyl chloride and a hydrazinodi-(methylamino) pyrimidine in the ratio of one mol of the former toapproximately two mols of the latter.

18. The method of preparing bis-[2,6-di- (methylamino) pyrimidyl-4hydrazinocarbonyl] which comprises effecting reaction, in an anhydrousliquid medium comprising pyridine, between oxalyl chloride and4hydrazino 2,6-di- (methylamino) pyrimidine in the ratio of one mol ofthe former to approximately two mols of the latter.

GAETANO F. D'ALE'LIO. JAMES W. UNDERWOOD.

Certificate of Correction GAETANO F. DALELIO ET AL.' It is herebycertified that errors appear in the printed specification of the abovenumbered patent requiring correction as follows: Page 1, second column,line 1, for meaninngs read meanings; l ne 3 1, for can read may; line61, strike out 2-hydrazino 4,6-di-(methylammo) pyrimidine page 2, secondcolumn, lines 18 to 23 inclusive,

for that portion of the formula reading:

Patent No. 2,339,060 January 11, 1944.

l l M l *1 arm :33 read 14 (RHN):-B:E L

l v l N J Page 3, second column, line 59, for ethane read ethane; line60, for beta-dis" read beta-bis; line 66, after methylaminof insert aclosing parenthesis; page 5, first column, line 53, after Y, insert onemtrogen atom of the grow 'ng; and that the said Letters Patent should beread with these corrections therein t at the same may conform to therecord of the case in the Patent Ofiice.

Signed and sealed this 18th day of April, A. D. 1944.

LESLIE FRAZER, Acting Commissioner of Patents.

